Views on Senolytic Drugs from the Pharmaceutical and Healthcare Industries
Senescent cells accumulate with age, most likely largely due to the growing incapacity of the aging immune system, slowing the pace of removal of senescent cells to the point at which their numbers grow. Senescent cells cause significant harm via their pro-growth, pro-inflammatory signaling, disrupting tissue structure and function. Senolytic drugs can selectively destroy senescent cells, largely by attacking mechanisms that provide resistance to the programmed cell death process of apoptosis, but a range of other approaches are under development. First generation senolytics have performed impressively in mouse models of a great many age-related conditions, rapidly reversing pathology and markers of age, and extending healthy life span. This makes their further development and availability in the clinic a matter of great interest.
Today's paper summarizes views on the development of senolytic drugs from a small panel of healthcare and pharmaceutical industry experts. The specific focus is the treatment of vascular disorders of aging, but the views are broadly applicable to the application of senolytic therapies to any age-related condition. I think the most interesting of their points of agreement is that there is a near complete lack of awareness of senolytics in the world at large. Many more clinical trials should be underway using the low cost senolytic combination of dasatinib and quercetin in terms of proving that it can work and finding useful human dosing strategies. It is entirely possible that most common age-related conditions don't have to be as severe as they are for the patients suffering them, but at the present pace it'll be years yet before any useful body of data emerges for that presently available senolytic therapy.
The field of targeting cellular senescence with drug candidates to address age-related comorbidities has witnessed a notable surge of interest and research and development. This study aimed to gather valuable insights from pharmaceutical experts and healthcare practitioners regarding the potential and challenges of translating senolytic drugs for treatment of vascular aging-related disorders. This study employed a qualitative approach by conducting in-depth interviews with healthcare practitioners and pharmaceutical experts. Participants were selected through purposeful sampling. Thematic analysis was used to identify themes from the interview transcripts. A total of six individuals were interviewed, with three being pharmaceutical experts and the remaining three healthcare practitioners.
Health providers and pharmaceutical experts viewed that there are certain challenges and considerations associated with measuring outcomes and assessing the effects of senolytic therapies. One of the primary issues is that measurable outcomes may not be immediate. Senescent cell clearance and subsequent tissue regeneration may take time to manifest noticeable effects. More importantly, to date there are no tools such as imaging probes or biomarkers that can measure the clearance of senescent cells from tissue. The lack of such simple tools not only hamper the identification of senolytic drugs which are truly specific for senescent cells but also for monitoring therapeutic efficacy.
Results from completed trials of dasatinib and quercetin using intermittent dosing (i.e., consecutive treatment for 2-3 days with 2-week resting period) appears to be tolerable, with mild to modest adverse effects. Hence, it is crucial to establish the safety profile and dosing regimen of new senolytic drugs to harness the beneficial effects whilst minimizing risks. From the healthcare practitioners' perspective, it is crucial to ensure that the new senolytic therapy does not interact with other medications, particularly for elderly individuals who are already managing multiple conditions and taking numerous medications. While drug interaction profiles may be available for repurposed drugs, it may not the case for newly developed senolytics. To this end, potential drug-drug interactions, particularly with medications taken by the elderly individuals for their comorbidities have yet to be examined in preclinical and clinical studies and warrant future investigations. In this regard, pharmaceutical experts of this study pointed out the importance of addressing both the selectivity and specificity of senolytics. Improving senolytics selectivity for senescent cells while sparring healthy non-senescent cells is crucial to minimize potential side effects.
The pharmaceutical sector demonstrates a positive inclination towards the commercialization of new senolytic drugs, albeit with concerns around safety and efficacy. Besides sharing the same outcome-related concerns as with the pharmaceutical experts, healthcare practitioners anticipated a lack of awareness among the general public regarding the concept of targeting cellular senescence to delay vascular aging-related disorders, and this knowledge gap extends to healthcare practitioner themselves as well.